In part 1 of this article, we covered the basics of cancer immunonutrition, cachexia prevention, and the amino acids arginine, citrulline, and glutamine. In this next half, we’ll continue to dive deeper into more nutrients and plant medicines that support a healthy immune system and healthy muscle growth for well-rounded cachexia prevention.
Adequate intake of high-quality absorbable protein is essential for optimum immune response and for enhancing lean muscle mass. Since antibodies are protein structures, low protein intake or poor protein utilization can lead to low antibody production and/or decreased surveillance, and a poor immune response. Proteins, a vital component of all human cells, are continually being built up and broken down into their amino acid building blocks.
A decline in protein synthesis (decreased anabolic activity) is the single most important indication of aging. As muscle mass diminishes, muscle strength begins its downfall. This catabolic breakdown process also results in decreased muscle strength, heart health, bone density, more obesity, impaired glucose metabolism, an increase in aging, and reduction in quality of life. Anabolic restoration with diet, exercise, rest, and botanical and nutritional formulations, is the core to my approach to health promotion, disease prevention, and healthy aging. The importance of enhancing cellular protein synthesis cannot be overstated. Aging causes a decline in protein synthesis that inevitably leads to disability and death. It is the single most overlooked and under-treated key factor to health that there is.
Undenatured Whey Protein Concentrate
Undenatured Whey Protein Concentrate (UWPC) is whey protein derived from milk during cheese production, processed to preserve its native protein structure. This preservation maintains the integrity of bioactive proteins which offer enhanced functional and immunological properties compared to denatured forms.
UWPC possesses the highest biological value of any protein source and provides balanced essential amino acids with exceptional protein quality metrics. It retains up to 99% of peptides undamaged, achieves the highest Protein Efficiency Ratio and Biological Value, and scores highest on the Protein Digestibility Corrected Amino Acid Score. UWPC is particularly rich in sulfur-containing amino acids (methionine and cysteine), and branched-chain amino acids.
UWPC is composed of alpha-lactoglobulin, beta lactoglobulin, bovine serum albumin, and immunoglobulins (IgG1, IgG2, secretory IgA, and IgM). Other components of the lactalbumin fraction include: enzymes, iron binding proteins, calcium, potassium, sodium, phosphorus, and vitamins A, C, B vitamins, folic acid, and biotin.,
Some health benefits associated with UWPC include: immune modulation, glutathione enhancement, intestinal health, anti-bacterial properties against pathogenic bacteria, weight management, liver health, and cardiovascular health., WPC has been shown to enhance cellular glutathione levels, a vital aspect of our cells’ protective ability., UWPC is rich in lactoferrin, an iron binding protein that is a vital element to the human body. Lactoferrin also assists the production of alpha-interferon, which has profound immune-stimulating actions. UWPC has also been found to inhibit cancer.,
With cancer incidence rising globally, UWPC has emerged as a promising supplemental intervention in oncology care. Multiple in vivo studies demonstrate UWPC beneficial effects for supporting cancer patients, including anti-cancer properties, particularly through apoptosis induction and antioxidant mechanisms.
In malnourished advanced cancer patients undergoing chemotherapy, receiving nutritional counseling, a 3-month supplementation with UWPC resulted in improved body composition, muscle strength, body weight, and reduced chemotherapy toxicity. ,
Undenatured Whey Protein Concentrate Improves Nutritional Status, Glutathione Levels, and Immune Function in Cancer Patients
A randomized, double-blind controlled trial examined UWPC supplementation effects on nutritional status, glutathione (GSH) levels, and immunity in 42 Thai cancer patients (41-63 years) receiving chemotherapy. Patients received either 40g WPC with zinc and selenium (n=23) or maltodextrin control (n=19) daily for 12 weeks.
UWPC supplementation significantly increased albumin (2.9%) and immunoglobulin G (4.8%) levels versus controls at week 12. GSH levels increased 11.7% in the intervention group compared to 6.0% in controls. Nutritional status scores also improved with WPC supplementation. These findings demonstrate that whey protein supplementation enhances GSH levels, nutritional status, and immune function in cancer patients undergoing chemotherapy, supporting its use in malnutrition prevention strategies.
UWPC in Cancer Immunonutrition: Therapeutic Potential and Clinical Applications
Key Findings
- Whey protein induces apoptosis through caspase cascade activation
- Lactoferrin-derived peptides demonstrate selective cytotoxicity against cancer cells
- Iron-binding properties prevent oxidative damage and reduce colon cancer risk
- Whey supplementation effectively combats cancer cachexia and muscle wasting
In clinical applications, UWPC supplementation shows exceptional promise for cancer cachexia management. Its high leucine content and ability to modulate IGF-I concentrations make it an effective, cost-efficient adjuvant therapy for muscle preservation and metabolic support in cancer patients.
Effect of Whey Protein Supplementation After Cancer Surgery
A 2024 study evaluated whether whey protein supplementation (WPS) improves postoperative outcomes compared to standard care in patients undergoing comprehensive surgical staging for gynecological cancer.
An open-label, randomized controlled trial at Rajavithi Hospital (November 2023-July 2024) enrolled 61 patients scheduled for comprehensive surgical staging. Participants were randomized 1:1 to WPS (n=30) or control (n=31). The UWPS group received 20g isolated whey protein at 6 pm pre-surgery and 6 am postoperatively. Primary endpoint was length of hospital stay (LOHS); secondary outcomes included gastrointestinal recovery, analgesic use, complications, and adverse events.
The UWPS group showed significantly shorter hospital stays (79.0±6.7 vs. 93.3±28.4 hours, P=0.021) and faster gastrointestinal recovery. (P0.05). No UWPS-related adverse events occurred.
Perioperative whey protein supplementation significantly reduces hospital stay and accelerates gastrointestinal recovery in gynecological cancer surgery patients while maintaining an excellent safety profile.
Branched-Chain Amino Acids (BCAAs)
BCAAs (leucine, isoleucine, and valine) are the main amino acids that make up muscle fibers. They provide nitrogen donors for glutamine, alanine, and aspartate formation while sparing muscle glycogen degradation during exercise and stress. They increase protein synthesis and minimize protein degradation, making them valuable in cancer cachexia management.
Both BCAAs and creatine may slow protein breakdown and enhance protein synthesis in skeletal muscle. Several studies have demonstrated that supplementation with these amino acids is a promising coadjuvant treatment for patients struggling with cachexia.
Beta-Hydroxy-Beta-Methylbutyrate (HMB)
What is HMB? Let’s start with its full name: ß-hydroxy-ß-methylbutyrate. Don’t worry about pronouncing it – we’ll stick with HMB! It’s a natural substance your body produces in muscle cells, and you can also find it in everyday foods like avocados, citrus fruits, cauliflower, and even catfish. Think of it as one of nature’s building blocks for maintaining strong, healthy muscles.
Why Your Body Loves HMB
Here’s what makes HMB fascinating: it’s like a guardian for your muscles. Imagine your muscles as a house – HMB helps with both construction (building new muscle) and maintenance (preventing breakdown). It’s particularly good at helping your body maintain what scientists call “lean body mass” or LBM – essentially, all the good stuff in your body that isn’t fat.
This matters more than you might think. Your lean body mass isn’t just about looking fit; it’s crucial for:
- Supporting your immune system
- Maintaining healthy skin
- Helping wounds heal properly
- Keeping your organs functioning well
- Maintaining physical strength and independence
The Science Behind the Magic
Recent research has shown something remarkable about HMB: it works through what scientists call “anticatabolic mechanisms.” In plain English? It helps prevent muscle breakdown while encouraging muscle growth. It’s like having a security system and a construction crew working together to protect and improve your muscles.
HMB, is actually a metabolite of leucine that demonstrates superior anti-catabolic effects compared to leucine itself. Research shows HMB is significantly more effective than leucine in stimulating muscle protein synthesis while simultaneously decreasing muscle protein breakdown. ,
Unlike anabolic hormones that induce muscle hypertrophy by increasing muscle protein synthesis, HMB is claimed to influence strength and lean body mass by acting as an anticatabolic agent, minimizing protein breakdown and damage to cells that may occur with intense exercise.
HMB Supplementation On Muscle Mass and Functional Outcomes In Cancer Patients
A systematic review of 15 studies (6 RCTs) examined HMB supplementation effects on muscle outcomes in adult cancer patients through December 2021. Most studies (80%) used 3.0 g/day Ca-HMB, typically combined with amino acids. Among higher-quality studies, HMB showed beneficial effects on muscle mass (4/4 studies), muscle function (2/2), hospitalization (3/3), and survival (5/7).
Implications For Muscle Wasting Prevention In Cachexia
Another randomized controlled trial evaluated HMB supplementation combined with resistance training for combating muscle wasting in older adults with sarcopenia, with direct relevance for cachexia management.
The intervention group was given: 3 g/day calcium HMB plus 12-week resistance training (3 sessions/week). The control group had: placebo plus identical training.
Primary endpoints included muscle strength and physical performance. Assessments were made at baseline, 12 weeks, and 1-year follow-up.
The HMB group showed significant improvements in balance (1.3 points, 95% CI: 0.3-2.4) and total physical performance scores (2.2 points, 95% CI: 0.4-4.0) versus placebo. Female participants demonstrated sustained handgrip strength gains (3.7 kg, 95% CI: 0.2-7.3) at 1-year follow-up.
HMB supplementation (3 g/day) combined with resistance exercise may effectively combat muscle strength decline in older adults with muscle wasting. Given mechanistic overlap between sarcopenia and cachexia, these results support the investigation of HMB for muscle wasting from cachexia as well.
Clinical Applications in Cancer
A randomized controlled trial using a combination of HMB (3g/d), L-arginine (14g/d), and L-glutamine (14g/d) in advanced cancer patients demonstrated significant body mass gain (0.95 ± 0.66 kg) and fat-free mass increase (1.12 ± 0.68 kg) over 4 weeks, compared to controls who lost weight and muscle mass. The mixture was effective in increasing fat-free mass of advanced (stage IV) cancer patients.
Studies performed with older people have demonstrated that HMB can slow the development of sarcopenia and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Many in-vitro and animal studies suggest that HMB can be effective in the treatment of muscle wasting from cachexia.
Omega-3 Fatty Acids
Omega-3 fatty acids, particularly EPA and DHA, provide anti-inflammatory effects by replacing pro-inflammatory arachidonic acid-derived mediators., Studies show omega-3 supplementation can stabilize weight and reduce pro-inflammatory cytokines in cancer cachexia.
Recent trials using parenteral fatty acids in surgical patients show immune benefits, anti-inflammatory effects, and direct anti-cancer actions. Essential omega-3 and 6 fatty acids from dietary linoleic acid or oily fish contribute to cachexia management. It has been hypothesized that the pro-inflammatory arachidonic acid can be partly replaced by DHA and EPA to stabilize weight and reduce pro-inflammatory cytokines.
Creatine
Creatine supplementation offers promising benefits for cancer patients struggling with muscle wasting and metabolic dysfunction. While traditionally known as a sports supplement, creatine’s fundamental role in cellular energy metabolism makes it particularly valuable during the metabolically stressed states common in cancer treatment.
By enhancing the body’s ability to transport and store cellular energy, creatine supplementation may help counteract the anabolic resistance and muscle loss that frequently accompany cancer and its treatments. This is especially important when oxygen delivery to tissues is compromised, a common occurrence in cancer patients.
Research suggests that increasing creatine availability in muscle tissue can support cellular metabolism, potentially helping cancer patients maintain muscle mass, recover from treatment-related fatigue, and restore anabolic processes essential for healing and strength recovery throughout their treatment journey.
Creatine supplementation enhances ATP resynthesis rates and improves bioimpedance parameters predictive of poor outcomes in cancer patients.,, Studies demonstrate creatine’s ability to enhance muscle growth, strength, and overall nutritional status in various clinical populations.
Creatine, as well as branched chain amino acids slow protein breakdown and enhance protein synthesis in skeletal muscle. Several studies have demonstrated that creatine supplementation is a promising additional treatment for cancer cachexia.
Creatine supplementation can strengthen skeletal muscle weakness in cancer patients on chemotherapy.
“Creatine MagnaPower” (MP) is a patented magnesium creatine chelate that provides the body with a readily available source of magnesium while also making the creatine more active by protecting it from cyclization. This patented mineral-amino-acid chelate contributes to an overall positive impact on many functions including a non-steroidal anabolic enhancing effect. Creatine MP will also provide rehydration and endurance to a person showing signs of physiological stress.
Creatine MP is one of the most important nutrients to be combined with anabolic botanicals, such as Rhaponticum carthamoides to provide the body with a one-two punch of plant compounds together with amino acid peptides for cellular restoration, to build the build body up for muscle recovery, as well as vital organ enhancement.
Research has also shown that creatine monohydrate slows body fat accumulation in children with acute lymphoblastic leukemia (ALL) during maintenance chemotherapy.
Vitamin D: The Sunshine Nutrient Your Muscles Can’t Live Without
Think of vitamin D as one of your body’s master keys, it unlocks so many doors to better health that scientists are still discovering new ones. While most of us know it’s important for strong bones, there’s a fascinating story about how this sunshine vitamin keeps your muscles strong and healthy that deserves attention.
Your muscles actually have receptors specifically designed to welcome this vitamin, like a lock and key. When your body doesn’t get enough vitamin D, these receptors start to lose their function. Imagine a key that’s slowly wearing down and no longer fits the lock properly. This breakdown can lead to muscle weakness and poor performance.
Inside your muscle cells, vitamin D works like an orchestra conductor, directing various essential processes. It helps your cellular powerhouses (mitochondria) produce energy more efficiently and fights off damaging oxidative stress. Think of vitamin D as both a power boost and a shield for your muscles. Vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration.
Vitamin D is also a crucial player in your immune system. It acts like a wise mediator, helping to calm down excessive inflammation while supporting your body’s natural defense mechanisms., It’s like having a skilled diplomat working inside your body, making sure everything runs smoothly and peacefully.
Research has shown that people with low vitamin D levels are more likely to experience age-related muscle loss. The good news? Studies suggest that vitamin D supplementation can help improve muscle strength and physical performance, particularly in older adults.
While sunlight is our natural source of vitamin D, many of us don’t get enough through sun exposure alone. Talk to your healthcare provider about checking your vitamin D levels and whether supplementation may be right for you. Be sure to check both vitamin D 25-OH and 125 diOH levels. I recommend a NaturizedTM and whole-food form of vitamin D combined with vitamin K, and red palm oil extract, a rich source of fat-soluble vitamin A from highly absorbable carotenoids, and the powerful tocotrienol form of vitamin E.,
Botanical Adaptogens and Specific herbs with Enhanced Anabolic Effects
Some of my favorite botanicals for enhancing anabolic health and assisting the immunonutrients include Rhaponticum carthamoides (Maral root), which has been traditionally used for increasing physical performance and recovery; Epimedium spp. (Horny Goat Weed), valued for its potential testosterone-supporting properties; Eurycoma longifolia (Tongkat Ali), known for its adaptogenic qualities and hormonal balance support; Tribulus terrestris (Puncture vine or Gokshura), widely studied for its potential effects on athletic performance and libido; Mucuna pruriens (Velvet Bean), rich in L-DOPA and supportive of dopamine production; Shilajit (Mumie), a mineral-rich compound that may enhance cellular energy production; and Cissus quadrangularis (Veld grape), traditionally used for bone health and recovery support. These botanicals work synergistically to support the body’s natural anabolic processes while providing essential micronutrients that complement immune system function.
Integrating Tonic Herbs with Immunonutrition: A Synergistic Approach
While targeted nutrients form the foundation of immunonutrition strategies, traditional tonic herbs offer a complementary dimension that can amplify therapeutic outcomes. The combination of evidence-based nutrients with adaptogenic herbs like ginseng and astragalus creates a comprehensive approach to immune system optimization during cancer treatment.
Mechanistic Synergy
Immunonutrients such as omega-3 fatty acids, glutamine, and vitamin D work at the cellular level to support immune function, reduce inflammation, and maintain gut barrier integrity. Tonic herbs operate through different but complementary pathways—For example, ginseng’s ginsenosides and astragalus’s polysaccharides act as immune modulators, helping to restore balance to dysregulated immune responses while supporting energy metabolism and stress adaptation.
Tonic herbs are traditionally used to enhance organ function, prevent functional decline in organs under stress, and support overall systemic health. These herbs interact with human biology to generate robustness, promote tissue restoration, and encourage self-regulation, and self-organization. Tonic herbs nourish, energize, correct, assist, build up, restore, and normalize functionality and strength.
Unlike herbs used for acute conditions, tonic herbs are more gentle in nature and meant to be taken for prolonged periods. They are not intended to directly treat disease, but rather to promote “robust health,” slow aging processes, and preserve, protect, and restore overall health.
Clinical Integration Strategy
Traditional herbal medicine can enhance conventional cancer treatments without interfering with their mechanisms. When properly combined, targeted immunonutrition and tonic herbs can:
- Enhanced immune cell reprogramming: Nutrients support M1 macrophage function while herbs facilitate the shift from tumor-promoting M2 phenotypes
- Improved treatment tolerance: Tonic herbs’ adaptogenic properties complement nutrients’ protective effects against chemotherapy-induced immunosuppression
- Sustained energy and recovery: Herbs support Qi (vital energy) while nutrients maintain metabolic pathways essential for immune cell activation
This integrative framework suggests that optimal cancer immunonutrition may require both precise nutritional intervention and the broader regulatory support that traditional tonic herbs provide, creating a more robust and adaptable immune response throughout treatment.
Immune Function and Perioperative Outcomes
Perioperative immunonutrition has been shown to correct impaired Th1/Th2 balance in cancer patients. A study of colorectal cancer patients found that preoperative oral supplementation with a formula enriched with arginine, omega-3 fatty acids and ribonucleic acid for five days significantly improved immune parameters. The supplemented group maintained the preoperative level of Th1/Th2 ratio, while the control group showed a gradual Th2 dominant shift.
Inflammatory Response Modulation
Oral immunonutrition during concurrent chemo-radiotherapy for esophageal cancer has been shown to reduce inflammatory cytokine levels. The levels of C-reactive protein (P = 0.001) and TNF (P = 0.014) increased more in the control group than in the treatment group.
Systemic and Mucosal Immunity
Perioperative immunonutrition modulates systemic and mucosal immunity in patients undergoing pancreaticoduodenectomy. Patients had significantly higher total lymphocyte count on the third postoperative day and a significantly greater rise in CD4/CD8 ratio from day 3 to day 7 postoperatively compared with standard nutrition-fed patients.
Mechanisms of Action
Immunonutrients work through multiple complementary mechanisms:
- Protein Metabolism: Enhancing protein synthesis while reducing protein breakdown ,
- Immune Function: Modulating T-cell responses, enhancing NK cell activity, and supporting antibody production , , ,
- Inflammatory Response: Reducing pro-inflammatory cytokines and promoting resolution of inflammation ,
- Intestinal Integrity: Maintaining mucosal barrier function and supporting enterocyte metabolism ,
- Antioxidant Systems: Supporting glutathione synthesis and cellular protection , ,
Eating Patterns and Anti-Cancer Immunity
The influence of diet on anti-cancer immune responsiveness has been extensively studied. Particular attention has been given to the gut microbiota and the impact of its composition on the immune system. Dietary patterns affecting immune function include adherence to healthy diets such as the Mediterranean, vegetarian, Japanese, or microbiota-regulating diets, and healthy fats (specifically coconut milk and oil, or medium chain triglycerides, also called MCTs), which have been demonstrated to lower the risk of developing several cancers and reduce associated mortality.
A habitual Mediterranean diet can play a role in improving responses to immune checkpoint blockade as therapy for advanced melanoma, according to findings from a cohort study published Feb 28, 2023, in JAMA Oncology.
The Mediterranean diet’s anti-inflammatory and immune-modulating properties make it particularly relevant for cancer prevention and treatment. Characterized by high intake of olive oil, fruits, vegetables, legumes, and nuts, with moderate fish consumption and limited red meat, this dietary pattern provides abundant monounsaturated fats, polyphenols, and fiber. De Filippis et al. demonstrated that adherence to the Mediterranean diet correlates with increased fecal short-chain fatty acids and beneficial bacteria (Prevotella, Firmicutes), while reducing trimethylamine oxide—a cardiovascular risk marker. The diet’s immunoprotective effects appear mediated through enhanced Lactobacillus, Bifidobacterium, and Prevotella populations and reduced pathogenic Clostridium, supporting improved lipid profiles and reduced systemic inflammation critical for cancer immune surveillance.
The dietary inflammatory index (DII) has been investigated as a potential predictor of hospitalization length among colorectal cancer patients treated surgically. Higher DII (meaning a diet with higher anti-inflammatory properties) was associated with shorter hospital stays, providing evidence for the role of dietary-related low-grade inflammation among surgical patients.
Optimal Protocols
The most effective immunonutrition protocols involve:
- Composition: Arginine + nucleotides + Omega-3 fatty acids
- Delivery: Enteral administration at 25-30 kcal/kg/day
- Timing: 5-7 days perioperatively
- Population: Particularly beneficial in malnourished patients
Nutrition optimization prior to surgery leads to improved surgical outcomes. Strategies to minimize hyperglycemia and insulin resistance by aggressive preoperative nutrition and carbohydrate loading may promote maintenance of a perioperative anabolic state, improving healing, reducing complications, and shortening the time to recovery of bowel function and hospital discharge.
Future Directions
While the Merderi Care approach to immunonutrition is powerful, more research is needed to more fully comprehend the details.
Future research should focus on:
- Optimal timing and duration of supplementation
- Individual nutrient vs. combination effects ,
- Integration with emerging cancer therapies
- Combining with botanical adaptogens, anabolic herbs, and tonic herbs
- Personalized nutrition approaches based on tumor type and patient characteristics ,
Conclusion
Immunonutrition represents an evidence-based approach to improving outcomes in cancer patients, particularly those undergoing surgery or experiencing cachexia., The combination of specific nutrients can significantly reduce complications, shorten hospital stays, and improve quality of life., As our understanding of nutrition-immune-system interactions grows, immunonutrition will likely become an increasingly important component of comprehensive cancer care.
