Hydroxycitrate is an over-the-counter supplement made from the plant Garcinia cambogia, and it has been promoted for weight loss. A review of trials found that it does indeed promote weight loss, but a small one.
I first came across a mention of hydroxycitrate in an article about potential calorie restriction mimetics. As calorie restriction is, at least at the moment, the gold standard for anti-aging protocols, and has reliably increased lifespan by as much as 50% in virtually all animals it has been tried on, scientists are naturally quite interested in it. The catch is that most people are unwilling or unable to restrict calories – which is one reason intermittent fasting has generated a lot of interest – and so many scientists are looking for calorie restriction (CR) mimetics: drugs or compounds that have some of the same physiological properties as calorie restriction.
Hydroxycitrate promotes autophagy
The property of hydroxycitrate that makes it a potential CR mimetic is that it promotes autophagy, the cellular self-cleansing process that rids cells of junk and that is so important in aging. “Similarly, either knockdown of ACLY or addition of hydroxycitrate (HC), its competitive inhibitor, also reduced cytoplasmic AcCoA levels, induced cytoplasmic protein deacetylation, and strongly stimulated autophagy in vitro.”
Oral administration of HC to WT mice for 2 days triggered a systemic autophagic response comparable to that induced by starvation. Prolonged treatment (2 weeks) with HC is known to cause significant weight loss, and this effect was not accompanied by reduced food intake. Surprisingly, weight reduction by HC was only observed in autophagy-competent wild-type mice, not in autophagy-deficient Atg4b−/− mice.
Hydroxycitrate induces autophagy strongly both in vitro, and in vivo in mice, comparable to that induced by starvation. This gives it the potential to be a powerful anti-aging drug.
It turns out that HC is also being used as part of a trio of OTC drugs that appear to be nearly a cure for cancer. Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.
Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.
An earlier study showed that this combination is virtually non-toxic, and what is more, as effective as chemotherapy.
The efficacy of this combination appears similar to conventional chemotherapy (cisplatin or 5-fluorouracil) as it resulted in significant tumor growth retardation and enhanced survival. This preliminary study suggests that this combination of drugs is efficient against cancer cell proliferation both in vitro and in vivo. A clinical trial is warranted.
And clinical trials have indeed begun.
The significance of the statement that these compounds “target the cellular metabolism not its DNA” lies in the metabolic theory of cancer, championed by Thomas Seyfried, which holds that cancer results from metabolic derangements, particularly in mitochondria, and not from DNA mutations. Seyfried is well known for promoting the use of ketogenic diets and intermittent fasting in cancer treatment and prevention.
Hydroxycitrate, as an autophagy promoter, could potentially boost the autophagy response to intermittent fasting. Naturally, being the experimenter that I am, I picked up some hydroxycitrate from Amazon the other day, and I intend to take it while doing my intermittent fast. Of course, you can’t feel autophagy, so I may have nothing further either to experience or report, but if in a few weeks time I feel 30 years younger, I’ll be sure to let you know.
14 Comments
Looks interesting – picked some up as well.
Any ideas on a good dose and frequency?
Maybe makes sense to take it a few times during the fasting window…
Hydroxycitrate can be toxic at high doses. The manufacturer recommends one dose of 300 mg before each meal, but I think that potentially could be too high. I’m going to limit myself, at least for now, to one capsule during a fasting window.
Can’t this stuff cause liver damage? I thought it was part of why Hydroxycut was pulled from the market, but I’m not sure.
See my comment above. Hydroxycut is still on the market: https://www.hydroxycut.com/ but as far as I can tell contains no hydroxycitrate. The cancer patients in the linked study got hydroxycitrate 500 mg, 3x daily; one of the got 500 mg IV, all with apparently no ill effects.
In terms of the timing of taking hydroxycitrate, I’m guessing the optimal time would be at the start of an (intermittent) fasting period, so as to hopefully maximize autophagy by both the effects of the fasting and the action of hydroxycitrate.
Any other ideas on the timing aspect?
I’m thinking the same, Stephen. I’ve been unable to find half-life values for it, but all instructions for it that I’ve seen say to take it 3 times a day, so I’m assuming half-life is low. Already, on a long (20 hour) fast I’ve taken it twice, once in the morning, and one in the afternoon. Manufacturer’s instructions on the bottle I got say do not exceed 6 doses a day.
If the half-life is indeed low, then perhaps it might be taken multiple times during a fasting period. I’m assuming that it would be less effective if taken during a feasted state – although I have no way to be sure of this assumption.
I can’t remember where I got this paper from but it’s in a folder for quercetin I saved.
“Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound.”
https://www.ncbi.nlm.nih.gov/pubmed/15685239
I hope I’m not repeating myself but here’s an idea. Why doesn’t the body recognize cancer and kill it? What is autophagy doing?
Maybe the body can’t see/get too the cells. There’s was a doctor n Sweden Bjorn Nordenstrom used 10-volt needle-like electrodes inserted into a tumor to destroy it. If you search for “cancer cure electrodes” you get a lot of links but what’s the mechanism for keeping the bodies defenses away from the cancer cell. Maybe it’s this, “Exclusion Zone Water” effects.
https://faculty.washington.edu/ghp/research-themes/water-science/
Apparently certain substances align water molecules into a crystalline shape. This pushes out all impurities so it’s just water. Yes the guy has heard of polywater he said he was extremely careful as he knows several researchers who’ve been ruined by studying water.
Maybe the quercetin is attacking the cancer and the ultrasound helps it get past the “exclusion zone”. Same with the electric fields overcoming the “exclusion zone”.
Could taking these substances and then shaking yourself do the same or would you need ultrasonics.
A lot of people talk about changing your ph to cure cancer. Could that be more of the same. Chemically changing the electropotential around the cells???
Yes I know I’m babbling but cancer does have a different electropotential than normal cells. I had read that before but when I heard about the exclusion zone it immediately made me think of the potential difference. The exclusion zone tech is being proposed for solar cells. Seems it get bigger and has a higher charge in sunlight. Good reason to get a little sun?
Anaerobic Glycolysis produces lactic acid. Injury signalling is by means of oxidants like hydrogen peroxide. Lactic acid neutralizes oxidants. Enough lactic acid can hence make the producing cancer “invisible” to the immune system. Yet a long shot.
Method: Change from glycolis promoting diet like high carb to high fat. Combine with stress like aerobic exercise to increase oxidants.
Do you feel 30 years younger?
Well, this morning I took 600 mg (2 capsules) of hydroxycitrate for my fast today. (I had been taking only one on fast days.) This dose was what I calculated to be about the human equivalent dose to that which caused massive autophagy in mice. (100 mg/kg /12). It killed my appetite, so I think something was happening. Interestingly, autophagy is required for hydroxycitrate-induced weight loss in mice; mice given autophagy inhibitors with it don’t lose weight, and the mice that did lose weight didn’t eat any less. That seems pretty wild to me. But, no, not feeling 30 years younger yet, but feeling pretty good.
So, it’s a few years later, are you still taking it and have you settled on a good dosage for you?
Hi PD – what’s the verdict on HC? Are you still taking it?
BTW, great update to your website!