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 631-769-2227
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Primal Flex
Sale

Primal Flex

$49.95

$49.95

THE MOST COMPLETE, NATURAL, FAST-ACTING JOINT SUPPORT FORMULA

● Promote overall joint health & mobility

● Formulated to maintain optimal inflammatory responses

● USA-made with natural Astaxanthin

● BioCell Collagen® + Hyaluronic Acid Matrix

● Type I collagen from eggshell membrane

● Boswellia Serrata & Turmeric root extract (95% curcuminoids)

● Gluten-free

SAVE UP TO 19% by selecting six bottles!

FREE SHIPPING on orders of $50 or more!

ORDER TODAY TO RECEIVE A FREE immune-boosting recipe e-book ($14.95 value)

Orders received by 4pm EST Mon-Fri will ship same day

For questions or phone orders call: 631-769-2227

THE MOST COMPLETE, NATURAL, FAST-ACTING JOINT SUPPORT FORMULA

● Promote overall joint health & mobility

● Formulated to maintain optimal inflammatory responses

● USA-made with natural Astaxanthin

● BioCell Collagen® + Hyaluronic Acid Matrix

● Type I collagen from eggshell membrane

● Boswellia Serrata & Turmeric root extract (95% curcuminoids)

● Gluten-free

SAVE UP TO 19% by selecting six bottles!

FREE SHIPPING on orders of $50 or more!

ORDER TODAY TO RECEIVE A FREE immune-boosting recipe e-book ($14.95 value)

Orders received by 4pm EST Mon-Fri will ship same day

For questions or phone orders call: 631-769-2227

FREE SHIPPING ON
ORDERS OF $50 OR MORE

ORDERS BY 4PM SHIP
SAME DAY

90-DAY MONEY-BACK
GUARANTEE

MADE
IN THE USA

FREE SHIPPING ON
ORDERS OF $50 OR MORE

ORDERS BY 4PM SHIP
SAME DAY

90-DAY MONEY-BACK
GUARANTEE

MADE
IN THE USA

6 CORE BENEFITS OF OUR

PRIMAL FLEX

FIGHT DISCOMFORT NATURALLY


Target the cause of joint stiffness and discomfort at the source.

You can finally relax knowing you can find relief naturally by addressing the root causes of your discomfort, rather than masking the real problem with synthetic painkillers and medications that can do more harm than good in the long run.

AYURVEDA INSPIRED FORMULA


Inspired by the most effective elements of Ayurvedic medicine, blending ancient holistic methods with the best of modern day techniques.

This Ayurveda-inspired formula uses pure ingredients like ashwagandha, turmeric, and boswellia to deliver effective and uniquely-formulated fast-acting joint support.

FIGHTS INFLAMMATION

Every ingredient has been carefully selected to decrease pain naturally and control chronic inflammation.

Tackle joint-related pain directly in a unique and effective way with one of the most complete natural joint support formulas on the market.

MULTI-COLLAGEN FORMULA

Collagen is the glue that holds your entire body together, especially your joints.

Your body naturally produces less and less essential collagen as you age, leaving your joint’s connective tissue at risk. Primal Flex keeps you moving with both Type I & II collagen, giving you everything you need to protect, repair, and strengthen your joints internally.

BIOCELL® COLLAGEN


Not all collagens are alike! BioCell® Collagen is a clinically studied ingredient, and is composed of naturally occurring hydrolyzed type II collagen peptides, chondroitin sulfate and hyaluronic acid - this is what makes BioCell®'s matrix unique, as it is not a blend of individual ingredients.

BioCell® Collagen promotes active joints, and healthy connective tissue. Various clinical trial support the safety, efficacy and bioavailability of BioCell® Collagen!

LOADED WITH VITAMIN C


Vitamin C does much more than help keep your immune system strong. High doses of this essential vitamin have been shown to help ease pain and reduce inflammation associated with many inflammatory joint diseases.

Primal Flex contains your daily recommended dose of vitamin C so that you can reap all of its benefits.

FIGHT Discomfort NATURALLY

 

Target the cause of joint stiffness and discomfort at the source.

You can finally relax knowing you can find relief naturally by addressing the root causes of your discomfort, rather than masking the real problem with synthetic painkillers and medications that can do more harm than good in the long run.

AYURVEDA INSPIRED FORMULA

 

Inspired by the most effective elements of Ayurvedic medicine, blending ancient holistic methods with the best of modern day techniques.

This Ayurveda-inspired formula uses pure ingredients like ashwagandha, turmeric, and boswellia to deliver effective and uniquely-formulated fast-acting joint support.

Supports Inflammatory Response

 

Every ingredient has been carefully selected to decrease discomfort naturally and maintain optimal inflammatory responses.

Tackle joint-related discomfort directly in a unique and effective way with one of the most complete natural joint support formulas on the market.

FIGHT Discomfort NATURALLY

 

Target the cause of joint stiffness and discomfort at the source.

You can finally relax knowing you can find relief naturally by addressing the root causes of your discomfort, rather than masking the real problem with synthetic painkillers and medications that can do more harm than good in the long run.

AYURVEDA INSPIRED FORMULA

 

Inspired by the most effective elements of Ayurvedic medicine, blending ancient holistic methods with the best of modern day techniques.

This Ayurveda-inspired formula uses pure ingredients like ashwagandha, turmeric, and boswellia to deliver effective and uniquely-formulated fast-acting joint support.

Supports Inflammatory Response

 

Every ingredient has been carefully selected to decrease discomfort naturally and maintain optimal inflammatory responses.

Tackle joint-related discomfort directly in a unique and effective way with one of the most complete natural joint support formulas on the market.

MULTI-COLLAGEN FORMULA

 

Collagen is the glue that holds your entire body together, especially your joints.

Your body naturally produces less and less essential collagen as you age, leaving your joint’s connective tissue at risk.Primal Flex keeps you moving with both Type I & II collagen, giving you everything you need to protect, repair, and strengthen your joints internally.

BIOCELL® COLLAGEN

 

Not all collagens are alike! BioCell® Collagen is a clinically studied ingredient, and is composed of naturally occurring hydrolyzed type II collagen peptides, chondroitin sulfate and hyaluronic acid - this is what makes BioCell®'s matrix unique, as it is not a blend of individual ingredients.

BioCell® Collagen promotes active joints, and healthy connective tissue. Various clinical trial support the safety, efficacy and bioavailability of BioCell® Collagen!

LOADED WITH VITAMIN C

 

Vitamin C does much more than help keep your immune system strong.High doses of this essential vitamin have been shown to help ease joint discomfort and stiffness.

Primal Flex contains all the vitamin C you need daily, so that you can reap all of its benefits.

MULTI-COLLAGEN FORMULA

 

Collagen is the glue that holds your entire body together, especially your joints.

Your body naturally produces less and less essential collagen as you age, leaving your joint’s connective tissue at risk.Primal Flex keeps you moving with both Type I & II collagen, giving you everything you need to protect, repair, and strengthen your joints internally.

BIOCELL® COLLAGEN

 

Not all collagens are alike! BioCell® Collagen is a clinically studied ingredient, and is composed of naturally occurring hydrolyzed type II collagen peptides, chondroitin sulfate and hyaluronic acid - this is what makes BioCell®'s matrix unique, as it is not a blend of individual ingredients.

BioCell® Collagen promotes active joints, and healthy connective tissue. Various clinical trial support the safety, efficacy and bioavailability of BioCell® Collagen!

LOADED WITH VITAMIN C

 

Vitamin C does much more than help keep your immune system strong.High doses of this essential vitamin have been shown to help ease joint discomfort and stiffness.

Primal Flex contains all the vitamin C you need daily, so that you can reap all of its benefits.

THE ULTIMATE JOINT RELIEF FORMULA

WITH HIGH-QUALITY TYPE I & II COLLAGEN, VITAMINS, AND AYURVEDIC HEALING HERBS
TO ELIMINATE JOINT PAIN AND INFLAMMATION.

  TRY RISK FREE  

NATURE'S BEST FOR YOUR HEALTH

COMPLETE INGREDIENT TRANSPARENCY

BIOCELL® HYDROLYZED TYPE II COLLAGEN

Backed by clinical trials, BioCell® Collagen has been shown to help the body maintain healthy connective tissues and flexible joints.

BioCell® Collagen has also been shown to aid musculoskeletal tissue during sports activity, making it a highly effective performance recovery supplement.

Hydrolyzed collagen is partially broken down collagen that increases the bioavailability of the protein.

AYURVEDA INSPIRED FORMULA

Primal Flex utilizes some of the most powerful aspects of Ayurvedic Medicine to create a truly unique and natural solution to joint support and repair.

Take advantage of multiple proven natural solutions to discomfort like turmeric, ashwagandha root, and boswellia.

These provide relief without the use of harmful synthetic painkillers and other drugs that do more to mask the issue than heal it.

EGGSHELL MEMBRANE TYPE I COLLAGEN

Eggshell membranes are composed of protein fibers found between egg white and the inner surface of the eggshell.

This protein has high percentages of certain amino acids such as arginine, glutamic acid, methionine, valine, cystine and proline.

Type I collagen from eggshell membrane is an effective and safe option for treatment of joint aches and stiffness.

SUGGESTED USE OF PRIMAL FLEX

HOW TO USE

Adults, as a dietary supplement, take two capsules daily, preferably with a morning or afternoon meal, or as recommended by your healthcare provider.*

For best results, combine with a healthy routine that includes balanced meals, exercise, water, and plenty of rest!

*capsules enlarged to show texture to every suggested “Servings per container”

Benefits

*capsules enlarged to show texture to every suggested “Servings per container”

SERVINGS PER CONTAINER

Each bottle of Primal Flex contains 30 servings per container. Recommended daily serving is two capsules per day.

*capsules enlarged to show texture to every suggested “Servings per container”

SUPPLEMENT FACTS

1. As your body adapts to your new supplement routine, it’s important to remember that every individual is different and health benefits may vary from person to person. Always consult with your physician before using this or any other product if you have a preexisting condition or take prescription medication.
2. If you are pregnant, nursing, taking medication, or have an existing condition, be sure to consult with your physician before taking this or any other dietary supplement.
3. Store in a cool, dry place. Keep out of reach of children.

* These statements have not been approved by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

*capsules enlarged to show texture to every suggested “Servings per container”

  • How to use
  • Benefits
  • Servings
  • Supplement Facts

Adults, as a dietary supplement, take two capsules daily, preferably with a morning or afternoon meal, or as recommended by your healthcare provider.*

For best results, combine with a healthy routine that includes balanced meals, exercise, water, and plenty of rest!

*capsules enlarged to show texture to every suggested “Servings per container”

*capsules enlarged to show texture to every suggested “Servings per container”

Each bottle of Primal Flex contains 30 servings per container. Recommended daily serving is two capsules per day.

*capsules enlarged to show texture to every suggested “Servings per container”

1. As your body adapts to your new supplement routine, it’s important to remember that every individual is different and health benefits may vary from person to person. Always consult with your physician before using this or any other product if you have a preexisting condition or take prescription medication.
2. If you are pregnant, nursing, taking medication, or have an existing condition, be sure to consult with your physician before taking this or any other dietary supplement.
3. Store in a cool, dry place. Keep out of reach of children.

* These statements have not been approved by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

*capsules enlarged to show texture to every suggested “Servings per container”

  • How to use
  • Benefits
  • Servings per container
  • Supplement Facts

Adults, as a dietary supplement, take two capsules daily, preferably with a morning or afternoon meal, or as recommended by your healthcare provider.*

For best results, combine with a healthy routine that includes balanced meals, exercise, water, and plenty of rest!

*capsules enlarged to show texture to every suggested “Servings per container”

*capsules enlarged to show texture to every suggested “Servings per container”

Each bottle of Primal Flex contains 30 servings per container. Recommended daily serving is two capsules per day.

*capsules enlarged to show texture to every suggested “Servings per container”

1. As your body adapts to your new supplement routine, it’s important to remember that every individual is different and health benefits may vary from person to person. Always consult with your physician before using this or any other product if you have a preexisting condition or take prescription medication.
2. If you are pregnant, nursing, taking medication, or have an existing condition, be sure to consult with your physician before taking this or any other dietary supplement.
3. Store in a cool, dry place. Keep out of reach of children.

* These statements have not been approved by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

*capsules enlarged to show texture to every suggested “Servings per container”

DON'T TAKE OUR WORD FOR IT

HEAR WHAT OUR CUSTOMERS ARE SAYING!

FREQUENTLY ASKED QUESTIONS

WHAT IS PRIMAL FLEX? 

Primal Flex is a fast-acting modern approach to supporting and maintaining healthy joints.

Featuring a cutting edge formula inspired by Ayurvedic medicine, Primal Flex is a fusion between the best ancient healing practices and modern technology.

WHY CHOOSE PRIMAL FLEX?

Primal Flex contains a unique blend of tried and true practices and modern ingredients. Primal Flex contains Type I & II collagen, turmeric, vitamin C, magnesium, ashwagandha, boswellia and more!

Primal Flex gives you everything you need to support and maintain healthy joints in one convenient, powerful, and effective package.

WHAT DOES AYURVEDA INSPIRED MEAN?

Ayurveda is one of the world’s oldest holistic (“whole-body”) healing systems in existence. The “sister science” to yoga, Ayurveda originated in India and incorporates a natural, whole body approach to wellness.

Primal Flex features many of the famous anti-inflammatory herbs used in Ayurveda, and combines them with powerful modern natural elements, like collagen. This creates a one-of-a-kind formula aimed at delivering support when and where you need it most.

WHAT IS THE BEST WAY TO USE PRIMAL FLEX?

You can use this product in the morning, afternoon, evening or even right before bed.

There is no specific time to take Primal Flex in general, but you will maximize the benefits of the product by taking it consistently. Find a time that works best for you!

IS PRIMAL FLEX SUITABLE FOR VEGANS AND OTHER SPECIAL DIETS?

Primal Flex contains both Type I & II collagen. The Type II Collagen is sourced from poultry, and the Type I from eggshell membrane. The capsules contain gelatin.

HOW LONG WILL A BOTTLE OF PRIMAL FLEX LAST?

One bottle of Primal Flex contains a one month supply. Primal Flex contains 30 servings per bottle. Each bottle contains 60 capsules, 2 capsules per serving.

ARE THERE ANY ALLERGY CONCERNS WITH THIS PRODUCT?

This product is manufactured in a facility that also processes tree nuts, peanuts, wheat, and soy. Always review the label for the most accurate information.

CAN I TAKE THIS PRODUCT IF I HAVE A MEDICAL CONDITION?

Primal Flex is intended for use by healthy adults 18 years or older.

We recommend that you consult your physician before use if you are taking any prescription or over-the-counter medications or are being treated for any medical condition.

HOW LONG WILL IT TAKE FOR MY BOTTLE OF PRIMAL FLEX TO ARRIVE?

Orders received before 4pm EST will ship the same day. Please allow 3-4 business days for your package to arrive. We will provide you with a tracking number once the package leaves our US warehouse.

HOW DO I STORE THIS PRODUCT? 

For maximum efficiency and shelf life, please store your product in a cool, dry place away from moisture, and outside of direct sunlight.

WHAT IS THE SHELF LIFE OF MY PRIMAL FLEX?

If stored properly and unopened, a bottle of Primal Flex will generally last around 2 years.

If opened, we recommend using the product within 90 days. Each bottle holds a 30-Day supply.

HOW MANY BOTTLES SHOULD I PURCHASE?

To take full advantage of our discounts, we recommend buying 6 to 12 bottles of Primal Flex. You are always protected by our 90-day money-back guarantee so you have plenty of time to enjoy the long term benefits of Primal Flex.

Please have a look at “What is the shelf life of my Primal Flex?” to learn more about the shelf life of Primal Flex.

What is Primal Flex?

Primal Flex is a fast-acting modern approach to supporting and maintaining healthy joints. Featuring a cutting edge formula inspired by Ayurvedic medicine, Primal Flex is a fusion between the best ancient healing practices and modern technology.

Why choose Primal Flex?

Primal Flex contains a unique blend of tried and true practices and modern ingredients. Primal Flex contains Type I & II collagen, turmeric, vitamin C, magnesium, ashwagandha, boswellia and more! Primal Flex gives you everything you need to support and maintain healthy joints in one convenient, powerful, and effective package.

What does Ayurveda inspired mean?

Ayurveda is one of the world’s oldest holistic (“whole-body”) healing systems in existence. The “sister science” to yoga, Ayurveda originated in India and incorporates a natural, whole body approach to wellness.

Primal Flex features many of the famous anti-inflammatory herbs used in Ayurveda, and combines them with powerful modern natural elements, like collagen. This creates a one-of-a-kind formula aimed at delivering support when and where you need it most.

What is the best way to use Primal Flex?

You can use this product in the morning, afternoon, evening or even right before bed. There is no specific time to take Primal Flex in general, but you will maximize the benefits of the product by taking it consistently. Find a time that works best for you!

Is Primal Flex suitable for vegans and other special diets?

Primal Flex contains both Type I & II collagen. The Type II Collagen is sourced from poultry, and the Type I from eggshell membrane. The capsules contain gelatin.

How long will a bottle of Primal Flex last?

One bottle of Primal Flex contains a one month supply. Primal Flex contains 30 servings per bottle. Each bottle contains 60 capsules, 2 capsules per serving.

Are there any allergy concerns with this product?

This product is manufactured in a facility that also processes tree nuts, peanuts, wheat, and soy. Always review the label for the most accurate information.

Can I take this product if I have a medical condition?

Primal Flex is intended for use by healthy adults 18 years or older. We recommend that you consult your physician before use if you are taking any prescription or over-the-counter medications or are being treated for any medical condition.

How long will it take for my bottle of Primal Flex to arrive?

Orders received before 4pm EST will ship the same day. Please allow 3-4 business days for your package to arrive. We will provide you with a tracking number once the package leaves our US warehouse.

How do I store this product?

For maximum efficiency and shelf life, please store your product in a cool, dry place away from moisture, and outside of direct sunlight.

What is the Shelf Life of my Primal Flex?

If stored properly and unopened, a bottle of Primal Flex will generally last around 2 years. If opened, we recommend using the product within 90 days. Each bottle holds a 30-Day supply.

How many Bottles should I purchase?

To take full advantage of our discounts, we recommend buying 6 to 12 bottles of Primal Flex. You are always protected by our 90-day money-back guarantee so you have plenty of time to enjoy the long term benefits of Primal Flex. Please have a look at“What is the shelf life of my Primal Flex?” to learn more about the shelf life of Primal Flex.

WE GUARANTEE

90-DAY MONEY-BACK GUARANTEE

We want you to be 100% satisfied with all the products you buy at the Primal Harvest Store. If you're not entirely happy with your purchase, we will refund your money in full, or exchange the products.

No questions asked. All you need to do is contact our customer support.

SHOP NOW

*These statements have not been evaluated by the FDA Food & Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease. The information provided by this website or this company is not a substitute for a face-to-face consultation with your physician and should not be construed as individual medical advice.

The testimonials on this website are individual cases and do not guarantee that you will get the same results. All content, including text, graphics, images and information, contained on or available through this web site is for general information purposes only.

Citations

Vitamin C and Immune Function

Anitra Carr-Silvia Maggini - https://www.ncbi.nlm.nih.gov/pubmed/29099763

 

Inflammation

https://lpi.oregonstate.edu/mic/health-disease/inflammation

 

Effect Of Vitamin C on Inflammation and Metabolic Markers in Hypertensive And/or Diabetic Obese Adults: a Randomized Controlled Trial

Mohammed Ellulu-Asmah Rahmat-Ismail Patimah-Huzwah Khaza'ai-Yehia Abed - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492638/

 

Office Of Dietary Supplements - Vitamin C

https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/

 

Office Of Dietary Supplements - Vitamin C

https://ods.od.nih.gov/factsheets/VitaminC-Consumer/

 

Immune-enhancing Role Of Vitamin C and Zinc and Effect on Clinical Conditions

Wintergerst DH; - https://pubmed.ncbi.nlm.nih.gov/16373990/

 

24-week Study on the Use Of Collagen Hydrolysate As a Dietary Supplement in Athletes with Activity-related Joint Pain

Kristine Clark-Wayne Sebastianelli-Klaus Flechsenhar-Douglas Aukermann-Felix Meza-Roberta Millard-John Deitch-Paul Sherbondy-Ann Albert - https://www.ncbi.nlm.nih.gov/pubmed/18416885

 

Hydrolyzed Collagen Intake Increases Bone Mass Of Growing Rats Trained with Running Exercise

Satoko Takeda-Jong-Hoon Park-Eriko Kawashima-Ikuko Ezawa-Naomi Omi - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750261/

 

Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women-a Randomized Controlled Study

Daniel König-Steffen Oesser-Stephan Scharla-Denise Zdzieblik-Albert Gollhofer - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793325/

 

The Role Of Vitamin C in the Treatment Of Pain: New Insights

Anitra Carr-Cate McCall - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391567/

 

Efficacy Of Turmeric Extracts and Curcumin For Alleviating the Symptoms Of Joint Arthritis: A Systematic Review and Meta-analysis Of Randomized Clinical Trials

James Daily-Mini Yang-Sunmin Park - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003001/

 

Connective Tissues

Author panel - https://www.sciencedirect.com/science/article/pii/B9780323341264000323

 

Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women-a Randomized Controlled Study

Daniel König-Steffen Oesser-Stephan Scharla-Denise Zdzieblik-Albert Gollhofer - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793325/

 

The Roles and Mechanisms Of Actions Of Vitamin C in Bone: New Developments

Patrick Aghajanian-Susan Hall-Montri Wongworawat-Subburaman Mohan - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833003/

 

Is There a Role For Vitamin C in Preventing Osteoporosis and Fractures? A Review Of the Potential Underlying Mechanisms and Current Epidemiological Evidence

Finck AA; - https://pubmed.ncbi.nlm.nih.gov/25412684/

 

Evaluation Of the Effects Of Biocell Collagen, a Novel Cartilage Extract, on Connective Tissue Support and Functional Recovery From Exercise

Hector Lopez-Tim Ziegenfuss-Joosang Park - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566464/

 

Biocell Technology LLC. (2015, April). BioCell Collagen® Feed your skin & joints™️. Retrieved May 15, 2020, from http://www.teknoscienze.com/Contents/Riviste/PDF/AF2_2015_RGB_4-5.pdf

 

Effects Of Biocell Collagen® on Connective Tissue Protection and Functional Recovery from Exercise in Healthy Adults: a Pilot Study

Hector Lopez-SM Habowski-JE Sandrock-AW Kedia-TN Ziegenfuss - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271657/

 

An Overview on Ashwagandha: a Rasayana (rejuvenator) Of Ayurveda

Narendra Singh-Mohit Bhalla-Prashanti de Jager-Marilena Gilca - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252722/

 

Beneficial Effects Of Natural Eggshell Membrane Versus Placebo in Exercise-induced Joint Pain, Stiffness, and Cartilage Turnover in Healthy, Postmenopausal Women

Kevin Ruff-Dennis Morrison-Sarah Duncan-Matthew Back-Cem Aydogan-Jason Theodosakis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822842/

 

Eggshell Membrane in the Treatment Of Pain and Stiffness from Osteoarthritis Of the Knee: a Randomized, Multicenter, Double-blind, Placebo-controlled Clinical Study

Kevin Ruff-Anne Winkler-Robert Jackson-Dale DeVore-Barry Ritz - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711914/