[toc]The most popular injectable fillers, like Juvederm and Restylane, are made from cross-linked hyaluronic acid (HA). You don’t need to be a plastic surgeon to know that they do an excellent job at giving people a youthful appearance. Here in Hollywood, these days they seem to be even more popular than Botox treatments.
When not in the cross-linked form, this molecule is naturally found in the skin. During youth, you have more. Its key benefit is the retention of moisture. (1)
It’s also found in your joints. In healthy knees, elbows, wrists, ankles, and other bone connections, the HA acts as a shock absorber and lubricant. A major cause of knee osteoarthritis is having too little, which contributes to stiffness. The lack of lubrication creates inflammation and that causes pain.
Given these facts, supplementing with hyaluronic acid capsules seems like a no-brainer for anyone past their young adulthood. After all, even if you’re healthy, you want to replenish the levels lost from the normal aging process!
Sorry, it’s not that simple.
Before you run over to Walmart or Walgreens to pick up a bottle, make sure you understand what it really is.
What is hyaluronic acid?
Hyaluronic acid is a large chain of sugar molecules. Known as a polymer, it’s made of two types of sugars; N-acetyl-glucosamine-6-phosphate and glucuronic acid. These are linked together like a pearl necklace, with each “pearl” in the chain alternating back and forth between the two sugars. It’s a heavy molecule, weighing up to millions of daltons.
This is what a fragment of the chain looks like on the molecular level. Here you only see two “links” in the chain, made of the two sugars bonded together. In actuality, the chain is very long, bulky, and heavy.
What does hyaluronic acid do?
Its main job is water retention. Whether natural or artificial, no other polymer in existence is known to hold as much moisture. Each gram of HA can hold up to 6 liters of water. That means it can hold up to 1,000x or more its own weight in water. This ensures moisture is retained in the skin, joints, and numerous other places throughout the human body. (2)
Weight/size compared to other supplements
For perspective, here are the weights of molecules found in several common dietary supplements:
Vitamin C (ascorbic acid) = 176 daltons (3)
CoQ10 = 864 daltons (4)
Curcumin = 368 daltons (5)
Alpha lipoic acid = 206 daltons (6)
Astaxanthin = 597 daltons (7)
Under 1,000 is to be expected for most supplements. Many scientists are skeptical as to whether anything much bigger can even be absorbed.
When it comes to the hyaluronic acid found in the body, they are categorized into the following three groups:
- low molecular weight: under 1,000,000 daltons (1 MDa)
- medium molecular weight: between 1,000,000 and 2,000,000 daltons (1 MDa to 2 MDa)
- high molecular weight: greater than 2,000,000 daltons (2 MDa)
The “low” descriptor is only relative to the larger hyaluronic acid molecules. Whether they are low, medium, or high, all of them are quite large. Their weight is up to thousands of times more than almost any other vitamin, mineral, or supplement that’s in your regimen. (8)
Some brands of hyaluronic acid supplements claim to be using “low molecular weight” sources. These supplements are typically not vegan or vegetarian. They are hyaluronic acid that comes from rooster comb. Those are the bright red parts on the heads of roosters.
The molecular weight of hyaluronic acid made from rooster comb is still quite high; 50,000 to 200,000 daltons. That’s according to U.S. patent #6,806,259.
While the actual claims of the application remain silent as to where the hyaluronic acid comes from, the description of the patent reports that commercial sources “are generally from umbilical cords and rooster combs.” (9)
Yes, human umbilical cords are another possible source.
Fortunately, neither supplements nor common dermal fillers use umbilical cords. Allergan’s Juvederm and Galderma’s Restylane use HA that has been biosynthesized using the fermentation of Stretococcus equi bacteria. Meanwhile, the origin of the HA used in most capsules and softgels continues to be the birds. (10)
In dermatology, there’s something called the 500 dalton rule. It’s a strongly supported theory that skin allergens larger than 500 daltons can’t be a contact sensitizer, because they can’t penetrate the skin’s surface and cause an allergic reaction. (11)
If that’s true for 500+ daltons, it explains why using hyaluronic acid for skin topically is far-fetched. Even with the “small” 50,000 dalton size coming from rooster combs, it can’t get inside. That said, it may offer a temporary benefit of increased surface moisture while it remains on the skin. Therefore, it’s use in face creams and lotions is not totally useless.
However when it comes to orally supplementing, how can we absorb it intact?
How much HA is in the body?
Hyaluronic acid is found throughout the entire body. Nearly 50% of the content is in the skin. All bones and cartilage contain it, with particularly high amounts in the hyaline cartilage, which covers the ends of long bones. High amounts are in synovial fluid, which is known as the motor oil of the body, because it is secreted by the synovial membranes around the joints.
Despite its prevalence throughout the body, in total there is very little.
Assuming a body weight of 154 lbs (70 kg) the average human has only 15 grams of hyaluronic acid in their body at a given time. Out of that, roughly 33% (5 grams) is broken down and replaced on a daily basis. (12)
In comparison, most dietary supplements contain 50 or 100 mg per serving. That’s a dosage which is 1-2% of what’s lost by your body daily, if you weigh 154 lbs.
If the HA was being absorbed and making its way to the proper locations, is this amount even adequate to replenish that which is lost by aging or injury?
How long it lasts
There’s a good reason why 33% of the hyaluronic acid in your body is replaced on a daily basis.
These molecules are very sensitive to free radicals. They’re constantly being degraded by them. (13)
This fact also explains, at least in part, why those who live an unhealthy lifestyle can appear to age faster and look older than one would guess. The skin on their face and body may be less plump, due to less retained moisture. In turn, this can accelerate the formation of fine lines and wrinkles.
Common things in your daily life which increase free radical production include drinking alcohol of any amount, UV exposure, high blood sugar, poor diet, and the list goes on. By increasing your free radicals, you may be decreasing the amount of hyaluronic acid in your skin and elsewhere.
Elsewhere may include your painful knee joints, too.
Something as innocent as drinking a glass or two of wine may seem totally unrelated to the health of your joints, but when you’re ramping up free radicals in your body, many things suffer with HA being just one of many.
What alcohol does to accelerate the physical signs of aging is actually comparable to what recreational drug usage does. It’s why both drinkers and drug users can look “weathered” for their age, if they have lived that lifestyle for an extended period of time. (14)
In addition to destruction by free radicals, throughout your body are hydrolyzing enzymes (hyaluronidase). These make hyaluronic acid molecules degrade or “go away” by adding water.
Given the fragility of the molecule, one has to question if hyaluronic supplements work after coming in contact with your stomach acid. Even when this gooey substance is in the parts of the body where it belongs, it’s degrading rapidly. One can only speculate as to the amount of degradation that takes place during digestion!
In short, there’s a constant battle on multiple fronts to degrade the HA that’s in your body.
The reason injectable dermal fillers last a long time – anywhere from 3 to 12 months – is because they are not normal hyaluronic acid. They are in a cross-linked form, to create what’s called a hydrogel.
These hydrogels have a continuous exterior to better resist degradation. It acts as a scaffold for their porous interior, which holds water. This makes them much less susceptible to your body’s hydrolyzing enzymes and the free radicals which constantly bombard them. (15)
Even with this fancy engineering, Juvederm and others still only provide a temporary replenishment.
In areas with high blood flow, like your lips, the amount of time they last is even shorter than in a less active area of the face, like your cheeks.
Of course this all begs the question, why aren’t there supplements made with cross-linked HA?
Even if there were, how would that benefit you when taking orally? Remember, there’s already this issue of the massive molecule size of regular HA, and the question mark of how could that possibly be absorbed and remain intact and flow throughout your bloodstream. Making the substance even bigger with a hydrogel only makes this feat all the more inconceivable.
Side effects of hyaluronic acid
If the hyaluronic acid in supplements is being absorbed, in theory there are several adverse reactions that may result:
1. May promote cancer growth
Higher amounts of hyaluronic acid correlate with malignancy and severity for certain types of cancer.
For this reason, it’s actually used as a tumor marker for monitoring cancer proliferation.
It’s unknown, but plausible, that intentionally adding HA to the tumors may promote their growth. (16) (17)
2. Promotes angiogenesis
Angiogenesis is the growth of new blood vessels. This may sound like a benefit but it’s actually a bad thing for cancer.
Without angiogenesis, cancers are limited in their growth because they need the formation of new blood supplies in order to grow.
This means there are at least two theoretical reasons as to why hyaluronic acid may be bad for you when it comes to cancer.
Age-related macular degeneration (AMD) also depends on angiogenesis. The development of new blood vessels (neovascularization) results in the death of photoreceptors, which in turn leads to vision loss. (18)
This new might be even worse with hyaluronic acid supplements, at least theoretically.
If those large molecules are being degraded into smaller HA fragments which then get absorbed, that size probably isn’t benefiting your beauty or joint pain, but research suggests that when they are between 4 and 25 disaccharides (units) in length, they have been found to “induce an angiogenic response” in animal research. (19)
3. May affect liver
Hyaluronic acid effects on the liver are unknown. Many dietary supplements and medications are processed by the liver and in theory, long term use of taking oral HA supplements daily may put extra stress on this organ. Since there is no proof of exactly what happens to these molecules during digestion, no one can say one way or another as to what effects they may or may not be having.
It is interesting to note that blood serum levels of hyaluronic acid are “accurate in predicting significant fibrosis, severe fibrosis, and cirrhosis” of the liver. Now this is a bit of a chicken vs. egg scenario… are higher levels of HA worsening liver disease? Or are higher levels merely a side effect of it? (20)
4. Can increase inflammation
In order for tissue repair to occur, inflammation must take place. During the early stages, HA is known to increase this effect.
While the high molecular weight has an overall anti-inflammatory effect, research suggests that the low molecular weight sizes are “a potent proinflammatory molecule.” (21)
Remember, many supplements specifically use low weight sources in the hopes that they offer bioavailability.
5. Could cause allergic reactions
Now to be clear, the pure molecules in and of themselves are a non-allergic substance. Similar to water, when this substance is identical to something that’s already in our bodies naturally, it’s not feasible that it could be allergen.
The danger comes from the fact that the origin of the hyaluronic acid used in many supplements comes from chickens. As such, proteins from the animals will be present.
This creates a risk for people with egg or poultry allergies. It’s why clinical studies have excluded people who have an allergy to chicken from participating. (22)
Do the supplements work?
While some of these side effects are specific to certain sources, even the best hyaluronic acid supplements face the challenge of unknown oral absorption and the fact that these molecules are so big, they would have to be fragmented smaller in order to travel through the circulatory system.
While they are believed to be safe and without noticeable side effects, that doesn’t guarantee that there isn’t something more sinister happening which can’t be detected.
Because of the many unknowns, claiming the supplements don’t work is also premature. It’s possible, though seemingly improbable, that they may benefit skin and joints in ways we don’t yet understand. Perhaps fragments of the HA travel to parts of the body and somehow, they connect to existing chains. Or perhaps they trigger the growth of new HA, collagen, elastin, or other things. However this is a far-fetched hypothetical.
Even when orthopedic doctors administer HA injections directly into the knee, a systematic review and meta-analysis of a large trove of data – spanning from 1966 to 2012 – drew this conclusion about the procedure (23):
“In patients with knee osteoarthritis, viscosupplementation is associated with a small and clinically irrelevant benefit and an increased risk for serious adverse events.”
Emphasis was added by us.
If you have joint pain or arthritis, there is much better evidence to advocate the use of curcumin supplements.
Cross-linked forms, like Juvederm, definitely do work when it comes to augmenting the size of soft tissue. Injections from a plastic surgeon – whether we want to admit it or not – are effective and likely safer, since the HA is isolated to the area it’s being injected (though what happens to it as it degrades over time isn’t clear).
If you want an oral supplement for skin, we are most impressed with the science on the L carnosine supplement.
Whether it’s your beauty or mobility, ultimately the best thing you can do is live a healthy lifestyle in all facets. If you’re not taking care of yourself, there’s no magic pill that can offset that.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.