Guggul also known as guggulu or gugulipid, is the oleo-gum resin procured from the white sap of various plants used in Indian Ayurvedic medicine. Two plants, Commiphora wightii (Indian bdellium or myrrh tree) and Boswellia serrata (Salai or Sallaki guggul or Shallaki from Indian olibanum or Indian Frankincense tree) are commonly utilized to prepare guggul (see Figure 1) ¹. Guggul is considered to have beneficial effects on multiple organ systems and is used to treat symptoms ranging from cholesterol-lowering, leg swelling and non-specific ulcers to diseases such as inflammatory bowel disease and aggressive malignancies ¹. Ancient script on medicine and surgery; Sushrut Samhita, describes that guggul when taken orally can cure internal tumors, malignant sores, obesity, liver dysfunction, intestinal worms, leucoderma, sinus, and edema ². Guggul has also been used as an Ayurvedic medicine for the prevention and treatment of various other diseases such as inflammatory bowel disease (IBD), ulcers, arthritis, cardiovascular diseases, diabetes etc ³. The main ingredients of guggul are guggulsterone, guggulsterol, boswellic acid and an ethyl-acetate soluble fraction called guggulipid consisting of highly bioactive phytochemicals ¹. A large number of test tube and in vivo studies have shown that guggul and its bioactive components act on multiple molecular targets leading to anti-inflammatory, antioxidant, and anti-apoptotic activity. This has led to the use of guggul for conditions such as arthritis, in fat-burners, for dyslipidemia and cardiovascular health. However, studies on the safety and clinical efficacy of guggul or its specific bioactive components are non-existent in published literature ². Grieco et al ⁴ described the case of a 63-year-old woman who consumed an over-the-counter lipid-lowering Ayurvedic product called ”Equisterol®” (containing guggul sterol, sitosterol, chlorogenic acid, policosanol, multivitamins and red yeast rice derived monacolin) for 6 months which was followed by the development of acute severe hepatitis. Liver biopsy revealed extensive necroinflammation with eosinophilic infiltration of hepatic lobules. Drug withdrawal and supportive care led to complete resolution of symptoms and normalization of liver tests within 10 days ⁴. The liver injury could have been due to the monacolin (with statins like activity) in red yeast, even though herb-yeast interaction was not ruled out ⁴. Yellapu et al ⁵ described a female bodybuilder who consumed a multi-ingredient fat burner supplement leading to acute liver failure. The supplements (Somalyz and Lipolyz, Species Nutrition, United States) contained usnic acid, L-carnitine, choline and ethanolamine, gamma-aminobutyric acid, vitamin E, green tea extract, guggulsterone Z, and guggulsterone E. Histopathology revealed massive hepatic necrosis and parenchymal collapse with a few areas of ductular regeneration. She underwent cadaveric liver transplantation and was discharged uneventfully. Even though various known plant-derived hepatotoxins (such as usnic acid, green tea extracts) were components of the supplement, the presence of guggul and its interactions were not ruled out ⁵. Guggul use has been implicated in the development of skin rash, diarrhea, headaches, nausea, and liver toxicity with high doses ⁶. As reported by Polavarapu and co-workers ⁶, a 44-year old male developed fatigue, malaise, and jaundice after consuming a fat-burner product (Lipo-6™ containing guggulsterones and green tea extract) for 1 month. Withdrawal of the herbal supplement resulted in complete clinical resolution after 1 month ⁶. Dalal et al ⁷ described a middle-aged woman who developed severe hepatocellular jaundice due to the intake of three different Ayurvedic herbal and Homeopathic medications (punarnaya mandur, extract from the Boerhavia diffusa and kanchnar guggulu, extract from Bauhinia variegate). Liver biopsy demonstrated mild portal chronic inflammation and interface activity with grade 3 bridging fibrosis, presence of ceroid-laden Kupffer cells, and conspicuous eosinophils suggestive of herbal-induced liver injury ⁷. Analysis of the retrieved herbal products and other medications did not reveal known hepatotoxic components, and the patient improved after a short follow-up ⁷. Guggul and its bioactive compounds have been implicated in possible and probable drug-induced liver injury with hepatocellular pattern of liver damage, which is usually self-limiting. However, there have been reports of acute liver failure requiring liver transplantation when guggul compounds have been part of multiherbal fat-burner products, a herb-herb interaction that remains unexplored ¹.

Figure 1. Guggul

Footnotes: (A) Commiphora and Gum guggul. (B) Boswellia and Salai guggul.

[Source ² ]

Chemical constituents of guggul

The guggul tree which belongs to the family Burseraceae, is mainly found in the dry regions of the Indian subcontinent mainly India, Pakistan and Bangladesh ². The oleogum resin of guggul tree (Commiphora mukul) is a yellowish substance that is tapped during winter and ~700–900 g of resin is obtained from each tree ⁸. The guggul or balsam or the oleo gum resin is found in the balsam canals in the phloem of the large veins of leaf and base of the stem. It is a complicated mixture of minerals, gum, terpenes, sterols (Guggulsterol -I,-II,-III,-IV,-V), essential oils, sterones (Z-, E-, M-guggulsterone, and dehydroguggulsterone-M), ferrulates, lignans, and flavanones. The ethyl acetate soluble fraction also known as guggulipid, consists of various bioactive components like diterpenoids, triterpenoids, steroids, lignans, and fatty tetrol esters. Based on the pH gradient, further fractionation yields 95% neutral, 4% acidic, and 1% basic fractions. The neutral fraction when subjected to further fractionation produces 88% non-ketonic and 12% ketonic fractions. A large number of steroids including the two isomers E-(cis-) and Z-(trans-) guggulsterone [4, 17(20)-pregnadiene-3, 16-dione] were obtained from the ketonic fraction. Nearly 5% guggulipid and 2% gum guggul by weight is present in the guggulsterone (see Figure 2A) ⁹.

Phenolics are common natural products found in plants and possess substantial antioxidant and anti-inflammatory effects. Various phenolic compounds such as hydroxybenzoic acid derivatives such as gallic acid, protocatechuic acid, gentisic acid, vanillic acid, p-hydroxy benzoic acid, syringic acid, ellagic acid, and cinnamic acid derivatives which include caffeic acid, chlorogenic acid, ferulic acid, sinapic acid, and p-coumaric acid are largely present in plants. These phenolic compounds are predominantly available in guggul as well, which in part contributes to its immense biological function against diverse human chronic diseases ¹⁰.

Guggulsterone is the only known antagonist of farnesoid X receptor (FXR). This farnesoid X receptor, also known as NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a bile acid receptor ². Bioinformatics studies (molecular docking simulation) revealed that guggulsterone binds to farnesoid X receptor (FXR) and nuclear factor-kappa B (NF-κB) and it docks into two non-canonical binding sites of farnesoid X receptor (FXR), helix 1-loop-helix 2 loop and parts of helix—helix 8 including helix 8-loop-helix 9 ¹¹. Different bile acids and chenodeoxycholic acids act as natural ligand for farnesoid X receptor, whose expression is elevated in the liver and intestine. When farnesoid X receptor binds to its ligand, it gets activated and reaches the cell nucleus, where it forms a heterodimer with RXR. This heterodimer binds to the hormone response elements on DNA and regulates various genes. Farnesoid X receptor activation downregulates cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol by inducing the expression of small heterodimer partner which in turn inhibits the transcription of CYP7A1 gene. While obeticholic acid, fexaramine, cafestol, and chenodeoxycholic acid act as agonist of farnesoid X receptor; guggulsterone, from the gum resin of guggul has also been confirmed to inhibit pro-inflammatory signals, together with transcription factor NF-κB ⁸. Another study reported that the inhibitory activity of NF-κB is due to the binding of guggulsterone to the RH domain of NF-κB precursor protein p105 containing important sequences for DNA binding and dimerization ¹².

Boswellia serrata, commonly known as salai guggul, Indian olibanum, loban, or kundur, belongs to the Burseraceae family and is found in dry mountainous regions of India, Northern Africa, and the Middle East. Burseraceae family includes 17 genera and 600 species of plants. The genus Boswellia has 25 different species distributed throughout the tropical regions. Boswellia serrata is one such medicinal plant which potential to combat various chronic disorders. The active pharmacological principle of the oleo gum resin from the trees of different Boswellia species is the boswellic acid ¹³. The gum resin of the Boswellia species mainly consists of mucus, resin acids, and volatile oil with different quantitative composition from species to species. The gum resin of salai guggul contains pentacyclic triterpenic acids, namely α-boswellic acids, β-boswellic acids, γ-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid (KBA), acetyl-11-keto-β-boswellic acid (AKBA), and tetracyclic triterpenic acids like tirucallic acids viz 3-oxotirucallic acid, 3-hydroxytirucallic acid, and 3-acetoxytirucallic acid (Figure 2B). Other oleo gum resin compounds which display biological activities are: betulinic acid, lupenoic acid, epi-lupeol, isoincensole, isoincensole acetate and 1-ursene-2-diketone-incensole acetate along with few other terpenes that can be found in volatile oil ¹³.

Figure 2. Chemical constituents of Commiphora (guggul) and Boswellia (Salai guggul)

Footnotes: (A) Commiphora (guggul) (B) Boswellia (Salai guggul)

[Source ² ]

Guggul uses

Guggulu has a long history of use in Ayurveda. Guggul has been used to treat obesity, hyperlipidemia, atherosclerosis, osteoarthritis, rheumatoid arthritis, gout, facial paralysis, sciatica, constipation, hemorrhoids, liver disorders, inflammation, cyst, cervical lymphadenitis, coronary thrombosis, anemia, diabetes, urinary calculus, increased frequency and turbidity of urine, and skin diseases ¹⁴. Boswellia extract is also used as a perfume and aroma (frankincense). In the United States, gum guggul extracts are marketed as dietary supplements that will help control serum lipid and cholesterol concentrations and stimulate the thyroid gland ¹⁵.

Several clinical trials have been conducted to evaluate the effect of guggul from Commiphora and Boswellia on various chronic disorders. Human studies on guggul has been found to be effective against different diseases such as asthma, breast fibroadenoma, chronic kidney disease, colitis, Crohn’s disease, fascioliasis, hepatitis C, hypercholesterolaemia, hyperlipidemia, metabolic syndrome, nodulocystic acne, arthritis, schistosomiasis, stress urinary incontinence etc (see Table 1) ². However, Boswellia serrata extracts have been not been approved for these uses in the United States.

The recommended daily intake of gum guggul extract formulations is highly variable among different manufacturers. The Indian Pharmacopeia bases its recommended daily intake levels of gum guggul extracts on the concentration of guggulsterones, such that consumption equates to 75 mg guggulsterones (25 mg, three times a day) ¹⁶. Assuming a daily intake of 75 mg of guggulsterones and an adult weight of 60 kg, average human daily consumption would equate to 1.25 mg guggulsterones/kg/day or 85.6 mg gum guggul extract formulation/kg/day based on the 1.46% guggulsterone content of the tested formulation. Boswellia serrata extracts are available over-the-counter in varying concentrations, the usual recommended dose being 250 to 500 mg two or three times daily. Boswellia serrata is also found in many multiingredient products advertised for joint health and gastrointestinal complaints.

Table 1. Clinical trials of guggul (Commiphora and Boswellia) against various chronic diseases

Disease	Dose	Pts (#)	Clinical outcome	References
Healthy volunteer	1 g ^b	10	Diminished efficacy	Dalvi et al ¹⁷
	125 mg, 2 capsules ^d	20	Increased pain threshold & tolerance force, well -tolerated	Prabhavathi et al. ¹⁸
	140 mg ^e	47	Effective	Chilelli et al. ¹⁹
	2 × 250 mg ^d	12	High and quick absorption	Riva et al. ²⁰
Asthma	900 mg/day; 6 weeks ^d	40	Improved disease condition	Gupta et al. ²¹
	500 mg/day ^d	32	Effective	Ferrara et al. ²²
Breast fibroadenomas	–^e	64	Reduction in fibroadenoma mass	Pasta et al. ²³
Chronic kidney disease (CKD)	516 mg ^e	16	Safe and tolerable	Moreillon et al. ²⁴
	–^b	60	Effective	Shelmadine et al. ²⁵
Colitis	900 mg/day; 6 weeks ^d	30	Safe and effective	Gupta et al. ²⁶
	1050 mg/day; 6 weeks ^d	–	Effective	Gupta et al. ²⁷
Crohn’s disease	–^d	102	Safe and effective	Gerhardt et al. ²⁸
	2,400 mg/day; 52 weeks ^d	108	Well-tolerated	Holtmeier et al. ²⁹
Fascioliasis	12 mg/kg/day; 6 days ^f	7	Safe, well-tolerated and effective	Massoud et al. ³⁰
	600 mg/day; 6 days ^f	1019	Safe and effective	Abo-Madyan et al. ³¹
Hepatitis C	–^a	15	Effective	Scholtes et al. ³²
Hypercholesterolemia	1,500 mg/day; 12 weeks ^b	205	Effective	Nityanand et al. ³³
	100 mg/day; 24 weeks ^f	61	Mild side effects	Singh et al. ³⁴
	1,000, 2,000 mg/day; 3 days ^b 103	–	Well-tolerated, caused dermatologic hypersensitivity	Szapary et al. ³⁵
	2,160 mg/day; 12 weeks ^b	43	Clinical magnitude is obscure	Nohr et al. ³⁶
Hyperlipidemia	–^f	–	–	Verma and Bordia ³⁷
	75 mg/day; 8 weeks ^a	–	Safe and effective	Beg et al. ³⁸
	2 g/day; 8 weeks ^b	59	Effective	Vyas et al. ³⁹
Metabolic syndrome	2 pills/day; 4 months ^b	78	Effective	Patti et al. ⁴⁰
Nodulocystic acne	50 mg/day; 3 months ^a	20	Reduced inflammatory lesions	Thappa and Dogra ⁴¹
Osteoarthritis	2 capsules, every 8 hours; 3 month-15 day wash-out-3 m ^e	42	–	Kulkarni et al. ⁴²
	500 mg ^b	30	Safe and effective	Singh et al. ⁴³
	999 mg/day; 8 weeks ^d	30	Well-tolerated	Kimmatkar et al. ⁴⁴
	100 or 250 mg/day; 90 days ^d	75	Safe and effective	Sengupta et al. ⁴⁵
	1000 mg/day ^e	30	Safe and well-tolerated	Kizhakkedath ⁴⁶
	6 capsules/day; 24 weeks ^e	440	Effective, improved knee function	Chopra et al. ⁴⁷
Polyarthritis	3600 mg/day ^d	78	No measurable efficacy	Sander et al. ⁴⁸
RT-related edema	4200 mg/day ^d	44	Effective, reduced cerebral edema	Kirste et al. ⁴⁹
Schistosomiasis	10 mg/kg/day; 3days ^f	204	Well-tolerated	Sheir et al. ⁵⁰
	600 mg/days; 6 days ^f	1019	Safe and effective	Abo-Madyan et al. ⁵¹
Skin damage in mammary carcinoma	Cream, twice/day ^d	114	Well-tolerated	Togni et al. ⁵²
Stress urinary incontinence	4 g/day, 8 weeks ^e	30	Effective	Arkalgud Rangaswamy et al. ⁵³

Footnotes: (a) Gugglusterone; (b) Guggul; (c) Formulation of guggul; (d) Boswellia; (e) Formulation of Boswellia; (f) Commiphora.

Guggul health benefits

Arthritis

Arthritis is mainly caused due to inflammation of joints, the tissues surrounding the joints and other connective tissues. Osteoarthritis is the most common form of arthritis which affects a wide range of people across all the places. As guggul has been reported to exhibit high affectivity against arthritis pre-clinically; hence, its effect was evaluated in the clinical setting as well. In one such study, 30 patients with arthritis were treated with gum guggul for 1 month which resulted in remarkable improvement in the total scores of Western Ontario and MacMaster Osteoarthritis Index and condition of the patients ⁴³. Another study was conducted by Kimmatkar et al. ⁴⁴, to check the safety, tolerability, and efficacy of Boswellia serrata (Salai or Sallaki guggul) extract in 30 patients with knee osteoarthritis. The patients receiving drug treatment reported a decrease in knee pain and swelling of the knee joint as well as increased knee flexion and walking distance.

Asthma

Asthma is a chronic multifactorial inflammatory disease of the respiratory tract and is one of the major health concern. Notably, Boswellia guggul has been found to be effective in the treatment of this disease. In a clinical study, 40 patients having 23 males, and 17 females in the age range of 18–75 years, suffering from bronchial asthma were treated with 300 mg of gum resin thrice daily for a period of 6 weeks ²¹. This led to improved prognosis in around 70% of the patients as various signs and symptoms of bronchial asthma like rhonchi, dyspnoea, and attacks disappeared upon treatment ²¹.

Breast fibroadenomas

Breast fibroadenoma accounts for the majority of breast lumps in young women. Boswellia serrata (Salai or Sallaki guggul) was found to exert beneficial effect against breast fibroadenomas as evidenced by a study conducted by Pasta and group ²³. They showed that treatment with the combination of Boswellia, betaine, and myo-inositol resulted in decreased fibroadenoma dimension in young women without exerting any toxic effects. The combination also resulted in reduced fibroadenoma volume in 38.8% of the patients in the experimental group, whereas the same was observed only in 17.85% patients in the placebo group ²³.

Cardiovascular diseases

Cardiovascular diseases is a group of diseases which involves the heart and the blood vessels is one of the most common causes of death across the globe. Notably, guggul presents a potent remedy for cardiovascular diseases. For example, Singh and group ⁵⁴ conducted a study to evaluate the cardioprotective benefits of guggul by enrolling 200 patients suffering from ischemic heart disease. The patients were treated with the combination of gum guggul and Inula racemosa for 6 months which resulted in the reduced levels of total cholesterol, triglyceride, and total blood lipids in the patients. It also restored the normal electrocardiogram (ECG) in 26% of the patients, showed improvement of ECG in 59% of the patients and lessened the chest pain in 25% of the patients ⁵⁴.

Chronic kidney disease

Chronic kidney disease (CKD) is a progressive disease where occurs due to enhanced inflammation and oxidative stress leading to reduced kidney function. Studies have indicated Boswellia serrata (Salai or Sallaki guggul) in combination with Curcuma longa as an effective regimen to obtain reduced inflammation in patients with CKD which functioned via modulation of prostaglandin E2 (PGE2) ²⁵. Moreover, this regimen was found to be safe, well tolerated which also enhanced the levels of inflammatory cytokines in CKD patients ²⁴.

Diabetes mellitus

A large population of the world is affected by diabetes mellitus or type 2 diabetes. Several preclinical studies have shown that the gum resin of commiphora and boswellia are highly effective against this disease. In a clinical study conducted by Ahangarpour et al. ⁵⁵, it was observed that the treatment of patients with diabetes mellitus with Boswellia serrata (Salai or Sallaki guggul) gum resin (900 mg daily for 6 weeks orally) resulted in decreased risk factors associated with this disease. Further, the treatment also helped in maintaining fructosamine levels, hepatic enzyme activities, and to bring lipid profiles close to normal levels in the patients ⁵⁵.

Eczema and psoriasis

Eczema also known as dermatitis and psoriasis are caused mainly due to inflammation of the skin. Boswellia serrata (Salai or Sallaki guggul) has been found to exert effectiveness against eczema and psoriasis. A group of scientists revealed that Boswellia-based cream lessens the use of topical corticosteroids and can diminish the grade of erythema and the skin superficial symptoms ⁵². Furthermore, in a double blind study, the efficacy of a novel formulation of boswellic acid (Bosexil®) containing Boswellia serrata (Salai or Sallaki guggul) resin extract and lecithin was evaluated against both psoriasis and eczema. Improvement in psoriasis, scales (70% of cases), and erythema (50% of cases) was observed with Bosexil® compared to placebo. In addition, when eczema patients were administrated with Bosexil® formulation, it showed improvement in both erythema (60% of cases) and itch (60% of cases) of the patients without any case of waning ⁵².

Fascioliasis

Fascioliasis is a parasitic worm infection caused by the common liver fluke Fasciola hepatica and Fasciola gigantica. The formulation of myrhh, the gum resisn of Commiphora molmol was reported to be safe, well tolerated, and effective for the management of fascioliasis ³⁰. The formulated drug comprised of 8 parts of resin and 3.5 parts of volatile oils, all extracted from myrrh. They observed that 7 patients who were passing fasciola eggs in their stools displayed distinct improvement of the general condition, drop in the egg count, and improvement of all signs and symptoms with no adverse side effects after treatment with the drug ³⁰.

Gingivitis

Gingivitis, the inflammation of gingiva is a very common form of gum disease. Frankincense extract has been found to exhibit efficacy against gingivitis. A double blinded randomized placebo controlled trial was conducted among 75 female patients aged between 15 and 18 years with moderate plaque-induced gingivitis ⁵⁶. Six groups were randomly formed based on the administration of 0.1 g of frankincense extract, 0.2 g of its powder, placebo, and whether the patients have undergone scaling and root planning or not. Gingival index, plaque index, bleeding index, and probing pocket depth were measured on the 0, 7th, and 14th days of the study. Detailed analysis of the data revealed that scaling and root planning along with the application of frankincense extract or powder might cause significant decrease in inflammatory indices in comparison to the groups without drug therapy and scaling and root planning ⁵⁶.

Inflammatory bowel disease

Different clinical studies with guggul have shown its efficacy against inflammatory bowel disease which include colitis and Crohn’s disease. For instance, the gum resin of Boswellia serrata (Salai or Sallaki guggul) was found to be effective in the treatment of chronic colitis with minimal side effects in a clinical study conducted by Gupta et al ²⁶. In this study, the patients with chronic colitis were treated with gum resin from Boswellia serrata (Salai or Sallaki guggul) at a dose of 900 mg daily divided in three doses for 6 weeks. The treatment resulted in the improvement of stool properties, hemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes, and eosinophils in the patients ²⁶. Further, a double-blind, placebo-controlled, randomized, parallel study on 82 patients with Crohn’s disease was conducted where patients were given a new Boswellia serrata (Salai or Sallaki guggul) extract; Boswelan. In this trial, remission was observed in 59.9% of the actively treated patients. Additionally, this study also confirmed better tolerability of Boswelan in long-term treatment of Crohn’s disease (Holtmeier et al., 2011). Furthermore, leukotrienes play an important role in inflammation of the colon in ulcerative colitis. Sallai guggul gum resin is known to be specific, non-redox, and non-competitive inhibitors of 5-LOX, a crucial enzyme of leukotriene biosynthesis. Patients with grade II and III ulcerative colitis were treated with Boswellia serrata (Salai or Sallaki guggul) gum resin at a dose of 350 mg thrice daily for 6 weeks. Stool properties, histopathology, and scan microscopy of rectal biopsies, blood parameters including hemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes, and eosinophils showed slightly better improvement in Boswellia treated patients ²⁷.

Nodulocystic acne

Guggul is considered to be very effective in topical and oral complementary as well as an alternative medicine for the treatment of acne ⁵⁷. In a clinical study conducted by Thappa and Dogra ⁴¹, patients with nodulocystic acne were given guggulipid equivalent to 25 mg guggulsterone for 3 months, which resulted in progressive reduction in lesions in majority of patients. However, patients with oily faces displayed better response to guggulipid.

Guggul side effects

Guggul side effects are few and largely mild and transient gastrointestinal symptoms of nausea, diarrhea or constipation ⁵⁸. In most controlled studies, adverse events were no more frequent with Boswellia extracts than with placebo. In a previously conducted clinical trial, individuals were treated with a guggulipid formulation at doses of up to 150 mg guggulsterones/day for 8 weeks, with adverse reports limited to low incidences of diarrhea and the development of a hypersensitivity skin rash ⁵⁹. Boswellia serrata extract has not been linked to serum enzyme elevations during therapy, although there have been few prospective studies in humans that have reported on its effects on laboratory test results in any detail. In small trials, Boswellia extracts have appeared to be well tolerated with only minor and few adverse effects which have been similar in frequency among persons receiving placebo ⁵⁸. Despite wide scale use as an herbal supplement, Boswellia extract has not been convincingly linked to published instances of clinically apparent liver injury ⁵⁸. Boswellia is often included in multi-ingredient dietary supplements some of which have been implicated in liver injury, but a specific contribution from Boswellia to the injury could not be established. The frequency of hypersensitivity reactions to Boswellia is also not known.

Grieco et al ⁴ described the case of a 63-year-old woman who consumed an over-the-counter lipid-lowering Ayurvedic product called ”Equisterol®” (containing guggul sterol, sitosterol, chlorogenic acid, policosanol, multivitamins and red yeast rice derived monacolin) for 6 months which was followed by the development of acute severe hepatitis. Liver biopsy revealed extensive necroinflammation with eosinophilic infiltration of hepatic lobules. Drug withdrawal and supportive care led to complete resolution of symptoms and normalization of liver tests within 10 days ⁴. The liver injury could have been due to the monacolin (with statins like activity) in red yeast, even though herb-yeast interaction was not ruled out ⁴. Yellapu et al ⁵ described a female bodybuilder who consumed a multi-ingredient fat burner supplement leading to acute liver failure. The supplements (Somalyz and Lipolyz, Species Nutrition, United States) contained usnic acid, L-carnitine, choline and ethanolamine, gamma-aminobutyric acid, vitamin E, green tea extract, guggulsterone Z, and guggulsterone E. Histopathology revealed massive hepatic necrosis and parenchymal collapse with a few areas of ductular regeneration. She underwent cadaveric liver transplantation and was discharged uneventfully. Even though various known plant-derived hepatotoxins (such as usnic acid, green tea extracts) were components of the supplement, the presence of guggul and its interactions were not ruled out ⁵. Guggul use has been implicated in the development of skin rash, diarrhea, headaches, nausea, and liver toxicity with high doses ⁶. As reported by Polavarapu and co-workers ⁶, a 44-year old male developed fatigue, malaise, and jaundice after consuming a fat-burner product (Lipo-6™ containing guggulsterones and green tea extract) for 1 month. Withdrawal of the herbal supplement resulted in complete clinical resolution after 1 month ⁶. Dalal et al ⁷ described a middle-aged woman who developed severe hepatocellular jaundice due to the intake of three different Ayurvedic herbal and Homeopathic medications (punarnaya mandur, extract from the Boerhavia diffusa and kanchnar guggulu, extract from Bauhinia variegate). Liver biopsy demonstrated mild portal chronic inflammation and interface activity with grade 3 bridging fibrosis, presence of ceroid-laden Kupffer cells, and conspicuous eosinophils suggestive of herbal-induced liver injury ⁷. Analysis of the retrieved herbal products and other medications did not reveal known hepatotoxic components, and the patient improved after a short follow-up ⁷. Guggul and its bioactive compounds have been implicated in possible and probable drug-induced liver injury with hepatocellular pattern of liver damage, which is usually self-limiting. However, there have been reports of acute liver failure requiring liver transplantation when guggul compounds have been part of multiherbal fat-burner products, a herb-herb interaction that remains unexplored ¹.

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